Insulin glargine is more potent in activating the human IGF-I receptor than human insulin and insulin detemir.

OBJECTIVE

To investigate whether human insulin (HI) and insulin analogues differ in their ability to activate the human IGF-I receptor (IGF-IR), the human insulin receptor A (IR-A) and the human insulin receptor B (IR-B) in vitro.

METHODS

HI, short-acting insulin analogues (insulin aspart; insulin lispro) and long-acting insulin analogues (insulin glargine; insulin detemir) were compared by using kinase receptor activation (KIRA) bioassays specific for IGF-IR, IR-A or IR-B, respectively. These assays quantify ligand activity by measuring receptor auto-phosphorylation upon ligand binding. HI and insulin analogues were tested in a range from 0.1 to 100 nM.

RESULTS

Short-acting analogues: Overall, short-acting insulin analogues did not differ substantially from HI, nor from each other. Insulin lispro was slightly more potent than HI and insulin aspart in activating the IGF-IR, only reaching statistical significance at 100 nM (p<0.01). Long-acting analogues: At <10 nM insulin glargine was as potent as HI in activating the IRs and IGF-IR. At 10-100 nM insulin glargine was significantly more potent than HI in activating the IR-B (p<0.05) and IGF-IR (p<0.001). Insulin glargine was more potent than insulin detemir in activating all three receptors (p<0.001). Insulin detemir was less potent than HI in activating the IRs at 1-10 nM (p<0.01) and IGF-IR at >1 nM (p<0.05).

CONCLUSIONS

Insulin glargine was more potent in activating the IGF-IR than HI and insulin detemir. Since KIRA bioassays do not mimic the exact in vivo situation, further research is needed to find out whether our data have implications for clinical use of insulin glargine.